Ionic and Metabolic Mechanisms in Pulsatile Insulin Secretion

Date: 09/13/2006

Lecturer(s):

Arthur Sherman (Laboratory of Biological Modeling, NIDDK/NIH)

Location:

University of British Columbia

Topic:

Insulin is secreted in pulses with a period of about 5 minutes from the
beta-cells of the pancreas. These pulses are in turn driven by
oscillations of cytosolic calcium. Two parallel streams of
investigation over more than two decades have studied metabolic
oscillations and ionic mechanisms as possible sources of the calcium
oscillations. We propose that the two are linked by a potassium
channel, K(ATP), that senses the ATP and ADP levels in the cell. This
directly transduces metabolic oscillations into oscillations of
membrane potential and calcium. However, calcium can also affect
metabolism by stimulating ATP-consuming pumps, by depolarizing the
mitochondria, and by directly activating Krebs cycle enzymes. A unified
model that combines the above elements and can thereby explain a
diverse set of experimental observations using only a few simple
assumptions will be presented